内酰胺酶β重编程脂质代谢，通过减弱mdm2介导的p53泛素化和降解来抑制子宫内膜癌的进展。

IF 3.8 3区生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Archives of biochemistry and biophysics Pub Date : 2025-02-01 DOI:10.1016/j.abb.2024.110287

Ting Zhou , Xiaorong Li , Fangfang Zhao , Jing Zhou , Binghui Sun

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引用次数: 0

摘要

背景：内酰胺酶β （Lactamase β， LACTB）抑制多发性恶性肿瘤的转移和进展。然而，对其在子宫内膜癌（EC）中的作用知之甚少。本研究旨在探讨LACTB在调控EC进展中的功能和可能的分子机制。方法：采用免疫组织化学染色、western blot和qRT-PCR法检测血清中LACTB的表达。采用异种移植小鼠模型、菌落形成、EdU和Transwell实验以及流式细胞术分析，在体内和体外研究了LACTB在EC中的作用。此外，为了评估LACTB对脂质代谢的功能，我们用尼罗红标记EC细胞中的脂滴。通过Western blot、免疫荧光染色、共免疫沉淀、泛素化、环己亚胺追踪实验和拯救实验来证实EC中LACTB、p53和MDM2之间的相互作用。结果：乳糜泻组织中LACTB表达下调。LACTB抑制EC细胞的恶性表型和重编程脂质代谢。此外，LACTB通过减弱mdm2介导的泛素化和p53的降解而显著上调p53。此外，沉默LACTB促进了EC细胞的恶性表型和脂质代谢的重编程；这与p53过表达相反。体内敲低LACTB通过下调p53促进EC的进展。结论：LACTB通过抑制mdm2介导的泛素化和p53的降解，抑制EC细胞的增殖和转移，并重编程脂质代谢。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

Lactamase β reprograms lipid metabolism to inhibit the progression of endometrial cancer through attenuating MDM2-mediated p53 ubiquitination and degradation

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Lactamase β reprograms lipid metabolism to inhibit the progression of endometrial cancer through attenuating MDM2-mediated p53 ubiquitination and degradation

Background

Lactamase β (LACTB) inhibits the metastasis and progression of multiple malignant tumors. However, little is known about its role in endometrial cancer (EC). Our study aimed to investigate the function and potential molecular mechanism of LACTB in modulating EC progression.

Methods

LACTB expression was measured via immunohistochemistry staining, Western blot and qRT-PCR. The role of LACTB in EC was investigated both in vivo and in vitro by employing xenograft mice models and using colony formation, EdU, and Transwell assays, along with flow cytometric analysis. In addition, to assess LACTB function on lipid metabolism, lipid droplets in EC cells were labeled with Nile red. Western blot, immunofluorescence staining, co-immunoprecipitation, ubiquitination assay, and cycloheximide chase assay and rescue experiments were performed to confirm the interaction between LACTB, p53, and MDM2 in EC.

Results

LACTB expression was downregulated in EC. LACTB inhibited the malignant phenotypes and reprogramed lipid metabolism in EC cells. Moreover, LACTB significantly upregulated p53 by attenuating the MDM2-mediated ubiquitination and degradation of p53. Besides, LACTB silencing facilitated the malignant phenotypes and reprogramed lipid metabolism in EC cells; this was reversed with p53 overexpression. LACTB knockdown facilitated EC progression via downregulating p53 in vivo.

Conclusion

LACTB repressed EC cell proliferation and metastasis, and reprogramed lipid metabolism via attenuating the MDM2-mediated ubiquitination and degradation of p53.

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来源期刊

Archives of biochemistry and biophysics 生物-生化与分子生物学

CiteScore

7.40

自引率

0.00%

发文量

245

审稿时长

26 days

期刊介绍： Archives of Biochemistry and Biophysics publishes quality original articles and reviews in the developing areas of biochemistry and biophysics. Research Areas Include: • Enzyme and protein structure, function, regulation. Folding, turnover, and post-translational processing • Biological oxidations, free radical reactions, redox signaling, oxygenases, P450 reactions • Signal transduction, receptors, membrane transport, intracellular signals. Cellular and integrated metabolism.